In the next week, re-exposure to the conditioned stimulus (drink), but now paired with placebo capsules, induced a suppression of immune functions as analyzed by the IL-2 and IFN-gamma mRNA expression, intracellular production, and in vitro release of IL-2 and IFN-gamma, as well as lymphocyte proliferation.

In vitro experiments, culturing fresh peripheral blood lymphocytes in 30 U/ml IL-2 (corresponding to the steady-state IL-2 concentration achieved in patients receiving IL-2 in our clinical trials), showed that the levels of IL-2 receptor released into the culture media exceeded the levels of cell-associated receptor, with both rising in parallel to the cytotoxic activity of the peripheral blood lymphocytes (PBL) against cultured tumor cells.

The response to tetanus toxoid was examined in 45 HIV-infected individuals and 11 controls using conventional lymphocyte proliferative assays concurrently with limiting dilution analysis utilizing the secretion of interleukin-2 as the measure of a response.

Proliferative inhibition was due to a suboptimal levels of IL-2secreted by lymphocytes, since the addition of recombinant IL-2 to the cultures reversed in a dose-dependent fashion the inhibitory effect of As.

These data show that patients with certain forms of uveitis have a measurable frequency of lymphocytes in the peripheral immunologic compartment capable of secretingIL-2 in response to autologous presentation of ocular autoantigen (S-antigen).

Based on their behavior in reversed-phase l.c. and their sodium dodecyl sulfate-gel-electrophoresis pattern, human IL-2 proteinsecreted by L cells showed a similar distribution of glycosylated (Mr 16 500) and nonglycosylated (Mr 14 500) forms as the natural protein secreted by human peripheral lymphocytes, whereas the hamster cell line secreted preponderantly the glycosylated forms.

Although TNT concentrations decreased in both P1 and P2 eluates relative to untreated baseline soil (BL) eluates, a recovery in lymphocyte growth/viability and IL-2secretion was seen with P2 but not P1 eluates relative to BL eluates.

Here we have compared the effects of cyclosporine on the phytohaemagglutinin (PHA) response of immature (cord) and mature (adult) lymphocytes using the following parameters of activation: (i) proliferation, measured by 3H-thymidine uptake; (ii) expression of cell surface IL-2 receptor; (iii) release of IL-2 into the supernatant.

Consistent with this observation, lung lymphocytes from patients with active sarcoidosis, a disease in which lung lymphocytes are spontaneously releasingIL-2, did express NK cell activity (P less than 0.01).

The underlying mechanisms of this tumor suppressive effect may be related with the activation of macrophages, followed by the indirect priming of lymphocytes to release effector molecules such as IL-2, to express IL-2 receptors, and to selectively suppress the synthesis of macromolecules in tumor cells.

The aim of this work was to study the in vitro effects of different concentrations of three novel aziridines, 2-hydroxy-methyl-1-(N-phtaloylglycyl) aziridine (aziridine 1), 2-hydroxy-methyl-1-(N-phtaloylalanyl) aziridine (aziridine 2) and 2-hydroxy-methyl-1-(N-phtaloylphenylalanyl) aziridine (aziridine 3), on the proliferative responses of human lymphocytes stimulated by mitogens (concanavalin A (Con A) and lipopolysaccharide (LPS)), and interleukin-2 (IL-2), interleukin-6 (IL-6) secretion.

S-adenosil-L-methionine did not affect lymphocyte proliferation while it reduced interleukin 2secretion upon phytohemagglutinin and pokeweed stimulation and interferon-gamma secretion upon all stimuli tested.

The results of our study confirm the immunosuppressive role of chenodeoxycholic acid on both secretive and proliferative lymphocyte functions and provide evidence of immunomodulatory activities of S-adenosil-L-methionine and its capacity to antagonize chenodeoxycholic acid-mediated inhibition of lymphocyte proliferation and interleukin 2secretion.

CONCLUSION: The decline of antibody titer and DTH response indicates that H. elymatica, by acting on the lymphocyte proliferation and IL-2secretion, inhibits both humoral and cell-mediated immune responses.

Taken together, these data suggest that PEMFs were able to modulate mitogen-induced lymphocyte proliferation by provoking an increase in utilization of IL-2, most likely acting on the expression of its receptor on the plasma membrane.

Using TNF-alpha as a model, we demonstrate that (a) the cytotoxic synergy occurs with both fresh human tumors and cell lines; (b) the degree of IL-2/TNF-alpha synergy, for most peripheral blood lymphocyte donors, is dependent upon the IL-2concentration used for activation with the most striking synergy observed at lower IL-2 doses; (c) synergy is specific for TNF-alpha and can be abrogated by neutralizing antibody against this cytokine; (d) addition of high-dose neutralizing antibody to IL-2 alone-stimulated peripheral blood lymphocytes can reduce the cytotoxicity capacity of these effectors suggesting an immunoregulatory role for endogenous TNF-alpha; and (e) TNF-alpha addition to IL-2-stimulated peripheral blood lymphocytes does not increase proliferation or cell recovery but does result in enhanced IL-2 receptor expression.

The findings suggest that Con A activation of snake lymphocytes in optimal seasonal conditions is associated with the secretion of a lymphokine analogous to the interleukin 2 (IL 2) of endothermic vertebrates.

Crude human decidual extracts containing up to 15.0 mg/l PP14 were investigated for their effects on the release of interleukin-2 (IL-2) and of IL-2 receptor (IL-2R) from phytohaemagglutinin (PHA) stimulated lymphocytes.

When PBMC were cultured up to 3 weeks with IL-2releasing LC89 cells (LC89/IL-2), the number of viable CD3+ and CD56+ lymphocytes was much greater than in cultures with parental cells or with LC89 cells transduced with the other cytokine genes.

Levels of serum sIL-2R (soluble interleukin-2 receptor) reflect the total amount of activated T lymphocytes in tumor infiltrating lymphocytes of cancer tissues and metastatic organs, because a part of alpha-chain of IL-2R is released into the bloodstream on the attachment of IL-2 (interleukin-2) to its specific IL-2R membrane.

The reproducible observation that virtually all malignant cells can be lysed by IL-2 stimulated lymphocytes in a manner directly related to the intensity of IL-2 administration encouraged the pursuit of aggressive, intensive clinical trials, especially in renal cell carcinoma and melanoma.

These results suggest that STPM inhibit lymphocyte proliferation by affecting one or several events occurring in the synthesis and/or expression of IL-2R P55 by a mechanism which is at least partially independent of its inhibitory effect on IL-2secretion.

We further show that defective IL-2secretion in response to melanoma antigens was not due to a T cell clone refractoriness induced by the culture, since one of these clones could be induced to secrete IL-2 by an antigen-expressing melanoma line, upon increased lymphocyte function associated antigen-3 expression induced by gene transfection.

Together these data suggest that defective IL-2secretion by many tumour-infiltrating lymphocytes clones in response to antigen presentation by melanoma cells in vitro is not exclusively due to the inability of these cells to provide an appropriate co-stimulation through the B7-1 molecule.

We have developed a simple culture assay system for measuring the in vitro effects of a chemical carcinogen, 3-methylcholanthrene (MCA), on certain activities of human peripheral blood lymphocytes: blastogenesis, cell-mediated cytotoxicity by natural killer cells, interleukin-2 production, lymphotoxin release and percent T-cell subpopulations.

If a mechanism of suppression in the mixed lymphocyte reaction is to reduce the synthesis/release of Il-2, memory cells may acquire their relative resistance to this suppression by virtue of the increased IL-2 sensitivity of this discrete subpopulation.